ISL1 overexpression enhances stem cell-mediated cardiac repair after myocardial infarction

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Overexpression of LIM-homeobox transcription factor islet-1 (ISL1) gene in human mesenchymal stem cells (hMSCs) increased angiogenesis and decreased apoptosis in a rat model of myocardial infarction (MI) post-cell transplantation. The study provides preliminary evidence for the use of ISL1 overexpression to enhance the efficacy of stem cell-mediated cardiac repair after MI.

Stem cell therapy has emerged as a promising treatment option for cardiovascular diseases. However, the low survival rate of transplanted stem cells has stood as a major hindrance for its widespread use in clinic. Apoptosis of stem cells, caused by limited blood supply to the transplantation site has been a major factor contributing to the low survival rate transplanted stem cells.

In the present study published in Stem Cell Research & Therapy, Dr Weiqiang Li and team at China’s Zhongshan Medical School explored a novel approach to enhance the viability of transplanted stem cells. ISL1 gene was previously identified as an attractive target for the treatment of myocardial dysfunction. Therefore, the team investigated whether overexpression of ISL1 in hMSCs could improve MI treatment outcomes.

Lentiviral vector encoding ISL1 was used to transduce hMSCs to generate ISL1-overexpressing hMSCs (ISL1-hMSCs). These cells were transplanted in a rat model of MI. In vivo results showed that transplantation of ISL1-hMSCs reduced the infarct size and improved cardiac function in rats transplanted with ISL1-hMSCs compared to rats treated with hMSCs alone. The greater potential of ISL1-hMSCs was attributable to increased cell survival after transplantation. It was also observed that ISL1-hMSCs reduced H2O2-induced apoptosis in vitro. In addition, conditioned medium from ISL1-hMSCs decreased the apoptotic effect of H2O2 on the cardiomyocyte cell line H9c2.

Taken together, these findings provide preliminary evidence for the use of ISL1 overexpression to enhance the survival and function of stem cells, thereby promoting the effectiveness of stem cell therapy after myocardial infarction.

Source: Xiang Q et al., ISL1 overexpression enhances the survival of transplanted human mesenchymal stem cells in a murine myocardial infarction model. Stem Cell Research & Therapy, February 2018. Reference